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1 HTLV 感染衛生署疾病管制局中區傳染病防治醫療網王任賢指揮官

2 HTLV isolation and identification HTLV-1 cell line from ex vivo PBMC and lymphonode cells from patient with T-cell cutaneous lymphoma (Poeisz, 1980) HTLV-2 spleen cells from patient with hairy cell leukemia (Kalyanaraman, 1982)

3 Retroviruses

4 HTLV infection Clinical and Epidemiologic relevance HTLV million carriers worldwide lifetime risk of progression to disease 1-5% HTLV-2 high prevalence in certain population groups low risk of progression to disease Mahieux, 1997; Salemi, 1999; Proietti, 2005

5 Geographical Distribution HTLV-1

6 Prevalence of HTLV-1 infection

7 Geographical Distribution HTLV-1 37% (Mueller, 1996)

8 Geographical Distribution HTLV-1 <5% (Manns, 1999)

9 Geographical Distribution HTLV-1 <5% (Manns, 1999)

10 Geographical Distribution HTLV-1 <5% (Gessain, 1996, Sarkodie, 2001)

11 Geographical Distribution HTLV-1 <6% (Murphy, 1991)

12 Geographical Distribution HTLV-1 <2% (Leon, 2003)

13 HTLV-1 infection in Brasil Serological screening in blood donors is mandatory since 1993 Estimate: 2,500,000 HTLV-1 carriers Source: Proietti, 2005

14 HTLV infection in Brasil Seroprevalence among Brazilian blood donors Proietti, 2002

15 HTLV infection Seroprevalence studies in Brazil Group Prevalence Author HIV asymptomatic carriers 1% Caterino-Araújo, 94 AIDS patients, SP 10% Casseb, 94 HIV/AIDS patients, Santos 13.4% Etzel, 2001 MSM, RJ 4% Cortes, 93 Commercial sex workers, RJ/MG Santos 9% 2.3% Cortes, 93 Bellei, 96 IDU, BA 35.2% Dourado, 98 Blood donors, SP RJ PE BA 0.15% % 0.6% 1.35% Ferreira Jr, 95 Carvalho, 97 Loureiro, 96 Galvão-Castro, 97 Pregnant woman, BA 0.84% Bittencourt, 2001 P0pulation-based survey Salvador, BA 1.76% Dourado, 2003

16 HTLV infection Seroprevalence studies in Brazil Nationwide sentinel study Pregnant women

17 Geographical Distribution HTLV % (Bittencourt, 2001; Dourado, 2003)

18 Geographical Distribution HTLV-2

19 HTLV-1 and HTLV-2 Genetic similasrity=65% Genotypic variants

20 HTLV transmission routes Sexual Blood-borne cellular components, IDU Mother-to-child breastfeeding

21 Sexual transmission Miyazaki cohort more efficient from infected males to female susceptible partner associated with long-term sexual partnerships associated with age of susceptible female partner postmenopausal women more vulnerable depends on local factors female genital tract Mueller, 1996

22 Sexual transmission HOST cohort, blood donors, USA 85 donors: follow-up every 2 years for 10 y 30 HTLV-1+ and 55 HTLV-2+ - steady sexual partnerships 4 soroconversions incidence = 0.6 / 100 PYFU (95%CI ) 2 HTLV-1 / 219 PYFU 0.9 / 100 PYFU ( ) 2 HTLV-2 / 411 PYFU 0.4 / 100 PYFU ( ) 2 cases M F and 2 cases F M Roucoux, 2005

23 MTCT Jamaican cohort associated with anti-htlv antibody titres (RR = 2.2/quartile) associated with HTLV proviral load in blood (RR = 1.9/quartile) and breast milk (RR = 2.34/quartile) dose-response relationship between risk of MTCT by breastfeeding and HLA class I concordance between mother and child longer survival of maternal cells? independent from maternal proviral load, antibody titres and income Hisada, 2002; Li, 2004; Biggar, 2006

24 HTLV transmission Unanswered question Few quantitative data on incident infections Frequencies vary among populations Frequencies vary in time Impact evaluation of preventive measures Challenge for prevention low adherence to longterm condom use in steady sexual partnership

25 HTLV-1 infection - Natural history - Acute infection Integration to genome 100% >95% Viral persistence life-long infection 100% Asymptomatic carrier HTLV-1-associated diseases <5%

26 HTLV-1 related diseases Adult T-cell leukemia/lymphoma (ATL/L) HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Inflammatory syndromes: uveitis, arthritis, polymyositis, Sjogren syndrome, infective dermatitis, pneumonitis

27 Prognostic markers HTLV-1 diseases development Proviral load (Taylor, 99) Monoclonal expansion of infected CD4+ T cells (Takemoto, 94) Genetic susceptibility (Jeffery, 99)

28 Prognostic markers Methodological limitations low prevalence of HTLV infection in many areas HTLV-related diseases are rare natural history long time interval to disease development few cohorts of asymptomatic carriers

29 Prognostic factors: ATL HLA genetic polymorphisms Ethnic and family clusters not related to HAM/TSP ATL-associated (vs. HAM/TSP and asymptomatic carriers) HLA-A*26, -B*4002, -B*4006 and -B*4801 less intense CD8+ anti-tax response Yashiki, 2001

30 Prognostic factors: HAM/TSP HLA genetic polymorphism - Kagoshima cohort protective haplotypes HLA-A*02, HLA-CW*08 associated with lower proviral load risk-associated haplotypes HLA-DRB-1, HLA- B54 Saito, 2005

31 Prognostic factors Clinical markers (infective dermatitis) Mode of exposure to HTLV infection

32 Prognostic factors Risk of ATL = higher for men infected at early ages varies according to age when infected Japan > Caribbean Risk of HAM/TSP = higher for women infected after weaning Caribbean > Japan

33 HTLV-2 related diseases Chronic myelopathy HAM/TSP-like Sensitive polyneuropathies Inflammatory myelopathies

34 Survival HOST study prospective cohort study blood donors, 5 centers, USA 152 HTLV-1+, 387 HTLV-2+, and 799 uninfected donors follow-up visits every 2 years since 1992 Survival median follow-up of 8.6 years 45 deaths HTLV-1 infection - unadjusted HR 1.9 (95%CI ); adjusted HR 1.9 (95%CI ) HTLV-2 infection - unadjusted HR 2.8 (95%CI ); adjusted HR 2.3 (95%CI ) Orland, 2004

35 Surviva HOST study Orland, 2004

36 Disease outcomes HOST STUDY HTLV-2+ donors acute bronchitis (incidence ratio [IR] = 1.68), bladder or kidney infection (IR = 1.55), arthritis (IR = 2.66), and asthma (IR = 3.28); pneumonia (IR = 1.82, 95% confidence interval [CI] 0.98 to 3.38) HTLV-1+ participants bladder or kidney infection (IR = 1.82), and arthritis (IR = 2.84) Murphy, 2004

37 懇請賜教

(D) 比例 (Ratio) 6. 狂犬病病毒是引起狂犬病的 : (A) 充分且必要條件 (B) 充分條件 (C) 必要條件 (D) 以上皆非 7. 某研究指出, 在 100 位憂鬱症患者中, 血型為 O 型佔 50%,

(D) 比例 (Ratio) 6. 狂犬病病毒是引起狂犬病的 : (A) 充分且必要條件 (B) 充分條件 (C) 必要條件 (D) 以上皆非 7. 某研究指出, 在 100 位憂鬱症患者中, 血型為 O 型佔 50%, 公共衛生核心課程基本能力測驗 105 年流行病學考試試卷一選擇題 ( 答案 4 選 1, 每題 2 分, 共 50 題 ) 1. 某大藥廠研發出一種新藥, 已經證實可以更有效地治癒高血壓患者, 也已經在台灣列為健保給付的用藥在目前其他與高血壓相關